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21.
SJ Smith CV Rahman PA Clarke AA Ritchie TW Gould JH Ward KM Shakesheff RG Grundy R Rahman 《Annals of the Royal College of Surgeons of England》2014,96(7):495-501
Introduction
The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.Methods
Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.Results
Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.Conclusions
Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models. 相似文献22.
Grigg AP; Roberts AW; Raunow H; Houghton S; Layton JE; Boyd AW; McGrath KM; Maher D 《Blood》1995,86(12):4437-4445
To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met- human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM- CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 micrograms/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 micrograms/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients. 相似文献
23.
O'Malley CJ; Rasko JE; Basser RL; McGrath KM; Cebon J; Grigg AP; Hopkins W; Cohen B; O'Byrne J; Green MD; Fox RM; Berndt MC; Begley CG 《Blood》1996,88(9):3288-3298
This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status. 相似文献
24.
Vijayendra Murthy David Sibbritt Jon Adams Alex Broom Emma Kirby Kathryn M. Refshauge 《Clinical rheumatology》2014,33(2):253-262
Back pain is a significant health service issue in Australia and internationally. Back pain sufferers can draw upon a range of health care providers including complementary and alternative medicine (CAM) practitioners. Women are higher users of health services than men and tend to use CAM frequently for musculoskeletal conditions. However, there remain important gaps in our understanding of women’s consultation patterns with CAM practitioners for back pain. The objective of this study is to examine the prevalence of use and characteristics of women who use CAM practitioners for back pain. The method used was a survey of a nationally representative sample of women aged 60–65 years from the Australian Longitudinal Study on Women’s Health. Women consulted a massage therapist (44.1 %, n?=?578) and a chiropractor (37.3 %, n?=?488) more than other CAM practitioners for their back pain. Consultations with a chiropractor for back pain were lower for women who consulted a General Practitioner (GP) (OR, 0.56; 95 % CI 0.41, 0.76) or a physiotherapist (OR, 0.53; 95 % CI 0.39, 0.72) than for those who did not consult a GP or a physiotherapist. CAM practitioner consultations for back pain were greater for women who visited a pharmacist (OR, 1.99; 95 % CI 1.23, 3.32) than for women who did not visit a pharmacist. There is substantial use of CAM practitioners alongside conventional practitioners amongst women for back pain, and there is a need to provide detailed examination of the communication between patients and their providers as well as across the diverse range of health professionals involved in back pain care. 相似文献
25.
K Nandar LW Ang J Tey L James KM Kyi Win CBE Chee OT Ng JL Cutter YT Wang 《HIV medicine》2018,19(1):59-64
Cross‐matching of records between Singapore's tuberculosis and HIV registries showed that 3.3% of individuals with tuberculosis (TB) were coinfected with HIV (2000?2014), the TB incidence among individuals with HIV infection was 1.65 per 100 person‐years, and 53% of coinfections were diagnosed within 1 month of each other. The findings supported joint prevention programmes for early diagnosis and treatment. 相似文献
26.
目的:观察视神经损伤动物模型在损伤后和不同时期视神经管减压后视觉诱发电位的变化,了解创伤性视神经损伤的手术时机与疗效的关系。方法:实验于2005-03/05在解放军南京军区南京总医院动物实验中心完成。①实验分组:30只新西兰白兔随机分为正常对照组、术后2d减压组、术后7d减压组、术后14d减压组、术后不减压组,每组6只。②造模:除正常对照组外,其余各组在视神经孔中塞入一细端为2mm直径的圆锥软硅胶,阻塞视神经孔,造成视神经的挤压伤。③指标检测:采用图形翻转视觉诱发电位检测损伤前、损伤后1h、减压前1h、减压后2周视功能变化,记录NPN曲线主波(P波)的绝对潜伏期、绝对波幅。正常对照组仅采集一组数据作为对照。结果:30只实验动物均进入结果分析。①正常对照组家兔图形翻转视觉诱发电位检查均引出典型NPN波型曲线,视神经挤压伤后1hNPN波形低阔扁平,P波潜伏期延长,波幅降低。②P波潜伏期:术后2d减压组减压后短于减压前[(71.25±8.51),(86.47±14.28)ms,P<0.05];术后7d减压组减压前后比较差异无显著性(P>0.05);术后14d减压组减压后明显长于减压前[(158.73±15.16),(116.35±17.13)ms,P<0.05]。术后2d减压组和术后7d减压组短于术后不减压组(P<0.01)。术后7,14d减压组和术后不减压组明显长于正常对照组(P<0.01)。③P波波幅:术后2d减压组减压后高于减压前[(5.25±0.78),(4.42±0.42)μV,P<0.05]。术后2d减压组减压后低于术后7d减压组、术后14d减压组(P<0.01),术后14d减压组低于术后7d减压组(P<0.05);术后7d减压组、术后14d减压组、术后不减压组低于正常对照组(P<0.01)。结论:神经元继发性损伤是视功能进行性下降的重要原因,视神经减压术有利于减轻视神经间接损伤,较早期(损伤后48h以内)减压可阻止轴突继发性损伤,避免视功能进一步下降,并在一定程度上逆转视功能的损害。 相似文献
27.
28.
MC Chau SF Leung KM Kam KY Cheung WH Kwan KH Yu KW Chiu TC Chan 《Journal of Medical Imaging and Radiation Oncology》2007,51(5):480-484
To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process. 相似文献
29.
Waterston–Cooley anastomosis may be carried out in patients with tricuspid atresia to provide pulmonary perfusion. It is associated with several complications, including preferential blood flow to the right lung, hypoplasia of the left pulmonary artery, obstruction of the anatomosis or rupture of pulmonary aneurysms. We study a patient with thrombosis in the pulmonary arteries following surgical construction of a Waterston shunt in childhood. Imaging findings and clinical symptoms are discussed with emphasis on echocardiogram‐gated multislice spiral CT. 相似文献
30.
Victoria KM Tay Robert Fitridge Mark LH Tie 《Journal of Medical Imaging and Radiation Oncology》2002,46(2):163-166
Demographic, clinical and laboratory data were retrospectively collected from records of 146 cases of CT fluoroscopy‐guided chemical lumbar sympathectomy for the palliation of inoperable peripheral vascular disease (PVD) between January 1997 and August 1999. Of these, 16% had claudication, 39% had rest pain and 44% had ischaemic ulcers or gangrene. Seventy‐three percent of elective cases were outpatients. At 3 months, 27 cases were lost to follow up, leaving 119 cases. Within 3 months, improvement, defined as doubling of the walking distance, cessation of rest pain or healing of ulcers, occurred in 30.3% of cases. No change was observed in 45.4% of cases and 24.3% of cases deteriorated. Patients with ulcers or gangrene had significantly poorer results than those without any ischaemic lesions, as only 19% versus 39% of patients improved (P < 0.05). The presence of hypertension, diabetes mellitus, hyperlipidaemia and smoking had no value in predicting clinical outcome (P > 0.05). There were no major complications noted. CT fluoroscopy‐guided chemical lumbar sympathectomy is safe and effective, with a complication rate of less than 1%, and efficacy of at least 30% measured within 3 months. It is a simple and minimally invasive procedure, easily performed on an outpatient basis. CT fluoroscopy‐guided chemical lumbar sympathectomy should be considered for all patients in the early stages of inoperable PVD. 相似文献